Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, United States of America; Women's Health Research Center, University of Mississippi Medical Center, United States of America.
Life Sci. 2019 Mar 1;220:44-49. doi: 10.1016/j.lfs.2019.01.048. Epub 2019 Jan 29.
The immune etiology of polycystic ovary syndrome (PCOS) is an intriguing area. However, whether there is alteration in the leukocyte populations in different tissues remain ambiguous.
To characterize the leukocyte populations of hyperandrogenemic female (HAF) rat tissues.
Female Sprague Dawley rats at 3 weeks of age were implanted subcutaneously with dihydrotestosterone (DHT) or placebo pellets. The rats were aged to 14-15 weeks and tissues were collected.
Peripheral blood (PB) and renal CD4 (P < 0.03, P < 0.007), Th17 (P < 0.05, P < 0.002), and CD4CD28 (P < 0.04, P < 0.001) were significantly increased in HAF rats compared to placebo, respectively, in spite of their lower percentage in the spleen. Although, the percentage of Treg T lymphocytes were significantly higher in the PB (P < 0.001) of HAF rats, the splenic (P < 0.01) and renal Treg cells (P < 0.03) were found to be significantly lower. Remarkably, HAF rats had higher renal mast cells (P < 0.00009) despite lower splenic (P < 0.002). The number of PB, renal, and splenic CD8 T cells and IgM-B cells in HAF rats remained unchanged.
Results from this study 1) provide the first evidence of significant alteration of T lymphocyte subsets and different leukocyte populations profile in a rat model of polycystic ovary syndrome, 2) demonstrate alteration of the immunological niche of blood, spleen, and kidney tissues in Hyperandrogenemia state in female rats, 3) imply potential immune system dysregulation in HAF rats which may suggest a link between excess androgen, chronic inflammation, and immune-mediated diseases in polycystic ovary syndrome patients.
多囊卵巢综合征(PCOS)的免疫病因学是一个有趣的领域。然而,不同组织中的白细胞群体是否发生改变仍不清楚。
描述高雄激素血症雌性(HAF)大鼠组织中的白细胞群体。
3 周龄雌性 Sprague Dawley 大鼠皮下植入二氢睾酮(DHT)或安慰剂丸。大鼠长至 14-15 周龄时采集组织。
与安慰剂相比,HAF 大鼠外周血(PB)和肾 CD4(P<0.03,P<0.007)、Th17(P<0.05,P<0.002)和 CD4CD28(P<0.04,P<0.001)显著增加,尽管其在脾脏中的比例较低。尽管 HAF 大鼠 PB 中的 Treg 淋巴细胞比例显著升高(P<0.001),但脾(P<0.01)和肾 Treg 细胞(P<0.03)的比例显著降低。值得注意的是,尽管 HAF 大鼠的脾脏(P<0.002)较低,但肾肥大细胞(P<0.00009)较高。HAF 大鼠的 PB、肾和脾 CD8 T 细胞和 IgM-B 细胞数量保持不变。
本研究结果 1)首次提供了多囊卵巢综合征大鼠模型中 T 淋巴细胞亚群和不同白细胞群体特征发生显著改变的证据,2)证明了在雌性大鼠的高雄激素血症状态下,血液、脾脏和肾脏组织的免疫微环境发生改变,3)提示 HAF 大鼠的免疫系统可能失调,这可能提示多囊卵巢综合征患者中过多的雄激素、慢性炎症和免疫介导的疾病之间存在联系。